In recent years, chemical reactions of living bodies have been closely examined in order to attempt to reproduce the chemical reactions of living bodies in a reactor. In living bodies, many biosynthetic reactions are naturally performed in the presence of enzymes as a catalyst in order to support life. Accordingly, living bodies easily produce compounds which are difficult to synthesize by chemical reactions. Knowledge of such reaction is becoming important for satisfying social requirements such as conserving energy and eliminating public nuisances. Reproducing such reactions will likely become an essential technique in chemical industries. The practical use of such reactions has already been found useful in the technical fields of hydrolysis and isomerization.
When carrying out a synthetic reaction (which is a particularly important reaction in biosynthetic reactions), ATP is required as an energy source or an auxiliary factor. In such reactions, ATP is consumed by decompressing into adenosine-5'-diphosphate (hereinafter referred to as ADP) or adenosine-5'-monophosphate after it serves as an energy source or an auxiliary factor. Accordingly, in order to industrially reproduce the synthetic reaction, it is necessary to supply ATP at a moderate price. However, ATP is a very expensive substance. Accordingly, it is important to convert ADP and AMP which are in a state after consumption and, particularly, AMP which is in a consumed state of the lowest energy level, into ATP.
Many studies concerning reproduction and conversion into ATP have been done. For example, since production of ATP is carried out by a glycolysis reaction in the living bodies, an attempt utilizing such a reaction is known in T. Tochikura, M. Kuwahara, S. Yagi, H. Okamoto, Y. Tominaga, T. Kano and K. Ogata, J. Ferment. Tech., 45, 511 (1967); H. Samejima, K. Kimura, Y. Ado, Y. Suzuki and T. Tadokoro, Enzyme Eng., 4, 237 (1978) and M. Asada, K. Yanamoto, K. Nakanishi, R. Matsuno and T. Kamikubo, Eur. J. Appl. Microbial. Biotechnol., 12, 198 (1981). The concept of the reaction is that reproduction and supply of consumed ATP are carried out using microorganisms, wherein AMP or adenosine is used as a raw material for ATP. However, since the AMP or adenosine is not a product after consumption of ATP, it is additionally added as an ATP source. As a result of this attempt, the conversion efficiency of AMP or adenosine into ATP is very inferior and side reactions are caused. Specifically, when utilizing glycolysis of microorganisms, negative result is only obtained concerning effective reproduction of ATP from AMP which is a product after consumption of ATP.
The use of an ATP conversion enzyme which is not a heat-resisting enzyme has been attempted. Langer et al. have reported process in converting AMP into ATP by means of adenylate kinase in rabbit muscles and acetate kinase in Escherichia coli in R. S. Langer, B. K. Hamilton, C. R. Colton, AlchE J., 23, 1 (1977); and U.S. Pat. No. 4,164,444. Further, reports have been made with respect to converting adenosine into ATP using adenosine kinase in addition to the above described two kinds of conversion enzyme in R. L. Baughn, O. Adalsteinsson and G. M. Whitesides, J. Am. Chem. Soc., 100, 304 (1978). Furthermore, Whitesides et al. have reported that, when the above-described adenylate kinase and acetate kinase are immobilized to Sepharose with cyanogen bromide to continuously convert AMP into ATP, the residual activity is only several percentages or less in the absence of a stabilizer and stability with the passage of time is remarkably inferior as described in G. m. Whitesides, A. Chmurny, P. Garrett and C. K. Colton, Enzyme Eng., 2, 217 (1974). Moreover, even if an immobilized enzyme is used and a stabilizer is added, the reaction requires a long period of time and conversion efficiency is not so high, and it cannot be utilized for operating under a level of chemical industry for a long period of time.
However, little is known with respect to the production of useful substances by the above-described synthetic reaction with reproducing ATP. There is a process which comprises reproducing ATP which was consumed when synthesizing glutathione by reacting glutamic acid, cystein and glycine with .gamma.-glutamyl cystein synthesis enzyme and glutathione synthesis enzyme, from ADP which is a product after consumption by a function of acetate kinase originated from Escherichia coli and using it again (as described in K. Murata, K. Tani, J. Kato and I. Chibata, Eur. J. Microbial Biotechnol., 10, 11 (1980)). However, this process does not provide any information with respect to converting the above-described AMP consumed to the lowest energy level into ATP, because it is only a process for reproducing ATP from /ADP.
A bioreactor for synthesizing a useful substance by continuously consuming ATP into AMP has been considered, and it has been highly desired to complete such a system as described in G. M. Whitesides, A. Chmurny, P. Garrett, L. Lamotte and C. K. Colton, Enzyme Eng., 2, 217 (1974).